The infectivity of the administration regimens will be assessed by thick film microscopy and PCR for P. falciparum DNA. [ Time Frame: Day 5 until day 21 or until treatment ] [ Designated as safety issue: No ]

Parasitology and parasite molecular biology tests: These tests are used to determine malaria parasites (thick blood smear and PCR). Both tests are performed at screening and then approximately every 12 hours during the period of intense observation from day 5 until day 21 or until treatment. Thereafter, these tests are performed during safety follow-ups at Days 28, 84, and 168. Turn over time for thick blood smear microscopy is < 2 hours to ensure timely treatment in case of a positive result. PCR results are available only after study completion.

Secondary Outcome Measures:

The time from parasite inoculation to first detection of blood stage parasitemia will be assessed by thick blood film microscopy. [ Time Frame: Day 5 until day 21 or until treatment ] [ Designated as safety issue: No ]

The safety of PfSPZ Challenge administered ID or IV and the resultant P. falciparum infection will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements [ Time Frame: Screening to Day 168 ] [ Designated as safety issue: Yes ]

These tests include full blood picture (complete blood count), liver enzymes and creatinine. All of these will be performed once at screening, Day -1 (day before challenge), Day 21 when no parasitemia occurs until then and day of malaria diagnosis. Lastly, these tests will also be performed during safety follow up at Days 28, 84 and 168.

TÜCHMI-001 is a single center, open label, randomized and controlled human pilot study to optimize controlled human malaria infection(CHMI) administered by PfSPZ Challenge. Volunteers will be inoculated with PfSPZ Challenge. Controls will receive the PfSPZ Challenge by ID administration. The remaining volunteers will receive the PfSPZ Challenge by IV administration. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens and dose-levels.

Volunteers and clinical investigators will not be blinded to group allocation, however laboratory investigators processing blood films and samples for PCR analysis will be blinded to group allocation.

Eligibility

Ages Eligible for Study:

18 Years to 45 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Healthy adults aged 18 to 45 years

Able and willing (in the Investigator's opinion) to comply with all study requirements

Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner if required

Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year)

Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local blood banking eligibility criteria

Written informed consent to undergo CHMI

Reachable (24/7) by mobile phone during the whole study period

Willingness to take a curative anti-malarial regimen

Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required

Answer all questions on the informed consent quiz correctly

A body mass index <35

A haemoglobin concentration ≥12 g/dl for women and ≥14 g/dl for men

Exclusion Criteria:

History of P. falciparum malaria

History of long term residence (>5 years) in area known to have significant transmission of P. falciparum

Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin)

Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period

Any other significant disease, disorder or finding which, in the opinion of the Investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624961